Processing unit fumes may have caused the blast at the Rosneft oil giant-owned Angarsk Petrochemical Company, according to emergency officials, The Moscow Times reported.
The Irkutsk regional branch of Russia's Emergency Situations Ministry said the explosion took place after midnight Moscow time.
Seismologists said residents of the city of Irkutsk 45 kilometers to the southeast and other nearby towns felt aftershocks from the blast.
“Many mistook it for an earthquake,” regional Governor Igor Kobzev wrote on the Telegram messaging app.
The fire engulfed an area of 2,500 square meters by the time it was contained.
Kobzev said two plant employees were killed and five were injured.
The Angarsk Petrochemical Company, the largest facility of its kind in eastern Siberia with an annual capacity of 10.2 million tons, said it is continuing to deliver fuel despite the deadly blast.
The Emergency Situations Ministry said it put out the fire five hours after it broke out.
Local investigative authorities have opened a criminal case into safety violations.
The explosion comes less than a month after a smaller fire broke out at the refinery on Nov. 27, causing no injuries.